Method and device for direct production of radio-isotope based cancer treatment pharmaceuticals

Patent metadata

Field	Value
Publication number	US-12090215-B2
Application number	US-202217649930-A
Country	US
Kind code	B2
Filing date	Feb 4, 2022
Priority date	Feb 4, 2022
Publication date	Sep 17, 2024
Grant date	Sep 17, 2024

Abstract

The present disclosure is generally related to methods, systems and devices for direct production of a radioisotope-based cancer treatment pharmaceutical directly from a corresponding non-radioactive drug molecule precursor by irradiating the non-radioactive drug molecule precursor using neutrons produced by an electronic neutron generator array or other neutron generator sources.

First claim

What is claimed is:

1. A method for producing a radioisotope pharmaceutical, the method comprising:
mixing a first aqueous solution comprising a non-radioactive Lu-176 isotope and a second aqueous solution comprising a target cell receptor binding peptide linked to a chelating agent to form a reacted solution comprising a Lu-176 complex of the Lu-176 isotope and the target cell receptor binding peptide linked to the chelating agent; and
irradiating the Lu-176 complex by a neutron flux generated by an electronic neutron generator and concurrently cooling the Lu-176 complex to convert the Lu-176 isotope in the Lu-176 complex to a Lu-177 radioisotope to form a Lu-177 based radioisotope pharmaceutical.

2. The method of claim 1 , wherein the target cell receptor binding peptide comprises or is a somatostatin receptor binding peptide selected from the group consisting of octreotide, octreotate, lanreotide, vapreotide and pasireotide, and wherein the chelating agent is selected from the group consisting of DOTA, DTPA, NT, EDTA, DO 3 A, NOC and NOTA.

3. The method of claim 2 , further comprising
heating the mixture of the first aqueous solution and the second aqueous solution to form the reacted solution comprising the Lu-176 complex.

4. The method of claim 3 , further comprising drying and purifying the reacted solution comprising the Lu-176 complex to form a non-radioactive isotope drug molecule precursor in a solid form, wherein irradiating the Lu-176 complex comprises irradiating the non-radioactive isotope drug molecule precursor in the solid form.

5. A device for direct production of a radioisotope pharmaceutical from a non-radioactive drug molecule precursor by irradiating the non-radioactive drug molecule precursor using a neutron flux generated by an electronic neutron generator array, the device comprising:
at least one electronic neutron generator configured to generate the neutron flux;
an insertion tube extending along an axis of the device, wherein the insertion tube is externally accessible via an insertion port;
a D 2 O moderator module surrounding and attached to an outer side surface of the insertion tube, the D 2 O moderator module housing D 2 O;
a borated water module surrounding and attached to an outer side surface of the D 2 O moderator module;
a metallic shielding module surrounding and attached to an outer surface of the borated water module; and
an irradiation module insert insertable in the insertion tube via the insertion port, wherein the irradiation module insert comprises:
an insertion rod for inserting the irradiation module insert in the insertion tube;
an irradiation chamber for housing an irradiation target material comprising the non-radioactive drug molecule precursor;
a removable nose configured to detachably connect to the insertion rod, wherein the irradiation chamber is housed in the removable nose; and
an insertion position lock ring configured to be placed on the insertion rod for locking the irradiation module insert with the insertion port to adjust a position of the irradiation chamber in the irradiation insertion tube.

6. The device of claim 5 , further comprising:
a radiation detector surrounding and attached to the irradiation chamber for detecting an irradiation level from the irradiation chamber; and
a temperature sensor coupled to the irradiation chamber for sensing a temperature of the irradiation chamber.

7. The device of claim 6 , further comprising a control unit configured to connect to the radiation detector and the temperature sensor.

8. The device of claim 7 , wherein the irradiation module insert further comprises:
an irradiation detector signal output configured to deliver a first signal of the detected irradiation level from the radiation detector to the control unit; and
a temperature sensor signal output configured to deliver a second signal of the sensed temperature from the temperature sensor to the control unit.

9. The device of claim 8 , wherein the at least one electronic neutron generator is configured to direct the neutron flux to a center of the insertion tube.

10. The device of claim 9 , wherein the irradiation module insert is configured to be placed into the insertion tube such that the irradiation chamber is exposed to the neutron flux from the at least one electronic neutron generator.

11. The device of claim 10 , further comprising a target cooling unit including a liquid coolant, wherein the target cooling unit is configured to circulate the coolant through the insertion tube for cooling the irradiation module insert inserted into the insertion tube to control temperatures inside the irradiation chamber.

12. The device of claim 11 , wherein the irradiation chamber is a hollow cylinder for housing the irradiation target material and comprises an outer side surface and top and bottom round surfaces, and wherein the irradiation detector is a hollow cylinder concentric with the irradiation chamber and configured to surround the entire outer side surface of the irradiation chamber without covering the top and bottom round surfaces of the irradiation chamber.

13. The device of claim 12 , wherein the control unit is configured to:
1) Receive the second signal; 2) adjust parameters of the target cooling unit to control the temperature inside the insertion tube and the irradiation chamber to maintain the temperature within a predetermined temperature range; 3) receive the first signal; 4) determine whether the detected irradiation level reaches a predetermined level; and 5) turn off the at least one electronic neutron generator when the detected irradiation level reaches the predetermined level.

14. The device of claim 5 , wherein the radioisotope pharmaceutical is selected from the group consisting of a Lu-177 based radioisotope pharmaceutical, an I- 131 based radioisotope pharmaceutical and a Y-90 based radioisotope pharmaceutical.

15. The device of claim 14 , wherein the non-radioactive drug molecule precursor is selected from the group consisting of a Lu-176 drug molecule precursor, a tellurium drug molecule precursor, and a Y-89 drug molecule precursor.

16. The device of claim 5 , wherein the radioisotope pharmaceutical is selected from the group consisting of Lu-177 dotatate, I-131 tositumomab, and Y-90 ibritumomab-tiuxetan, and wherein the non-radioactive drug molecule precursor is selected from the group consisting of Lu-176 dotatate, tellurium tositumomab, and Y-89 ibritumomab-tiuxetan.

17. The method of claim 2 , wherein irradiating the Lu-176 complex by the neutron flux generated by the electronic neutron generator and concurrently cooling the Lu-176 complex comprises irradiating and cooling the Lu-176 complex using a device, wherein the device comprises:
the electronic neutron generator;
an insertion tube extending along an axis of the device, wherein the insertion tube is externally accessible via an insertion port;
a D 2 O moderator module surrounding the insertion tube;
a borated water module surrounding the D 2 O moderator module;
a metallic shielding module surrounding the borated water module; and
an irradiation module insert insertable in the insertion tube via the insertion port, wherein the irradiation module insert comprises:
an insertion rod for inserting the irradiation module insert in the insertion tube; and
an irradiation chamber for housing the non-radioactive isotope drug molecule precursor; and

a cooling unit including a coolant, wherein the cooling unit is to circulate the coolant through the insertion tube for cooling the irradiation module insert inse

Assignees

• Westinghouse Electric Co Llc

Inventors

• Heibel Michael D
• Boyle James
• Paserba Kris

Classifications

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• A61K2123/00

  Preparations for testing in vivo · CPC title

• C07B59/008

  Peptides; Proteins · CPC title

• G21G1/06 Primary

  by neutron irradiation · CPC title

• A61K51/083

  the peptide being octreotide or a somatostatin-receptor-binding peptide · CPC title